System for treating a lung

ABSTRACT

A method for treating the lung during an acute episode of reversible chronic obstructive pulmonary disease such as an asthma attack. The method comprises transferring energy to an airway wall of an airway such that a diameter of the airway is increased. The energy may be transferred to the airway wall prior to, during or after an asthma attack. The energy may be transferred in an amount sufficient to temporarily or permanently increase the diameter of the airway. The method may be performed while the airway is open, closed or partially closed.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. application Ser. No. 09/999,851 filedOct. 25, 2001, which is a continuation-in-part application of U.S.application Ser. No. 09/296,040 now U.S. Pat. No. 6,411,852 B 1, acontinuation-in-part application of U.S. application Ser. No. 09/436,455filed Nov. 8, 1999 and a continuation-in-part application of U.S.application Ser. No. 09/535,856 filed Mar. 27, 2000 each of which isincorporated by reference herein in its entirety. U.S. application Ser.No. 09/999,851, is also a continuation-in-part application of U.S.application Ser. No. 09/349,715 now U.S. Pat. No. 6,488,673 B1 which isa continuation-in-part of U.S. application Ser. No. 09/003,750 now U.S.Pat. No. 5,972,026.

BACKGROUND

Asthma is a serious chronic condition affecting an estimated 10 millionAmericans. Asthma is characterized by (i) bronchoconstriction, (ii)excessive mucus production, and (iii) inflammation and swelling ofairways. These conditions cause widespread and variable airflowobstruction thereby making it difficult for the asthma sufferer tobreathe. Asthma further includes acute episodes or attacks of additionalairway narrowing via contraction of hyper-responsive airway smoothmuscle. Other obstructive diseases such as COPD may also have areversible component caused by one or more of the above mentioned threeelements.

Asthma generally includes excessive mucus production in the bronchialtree. Usually, there is a general increase in bulk (hypertrophy) of thelarge bronchi and chronic inflammatory changes in the small airways.Excessive amounts of mucus are found in the airways and semisolid plugsof mucus may occlude some small bronchi. Also, the small airways arenarrowed and show inflammatory changes. The reversible aspects of COPDinclude partial airway occlusion by excess secretions, and airwaynarrowing secondary to smooth muscle contraction, bronchial wall edemaand inflammation of the airways.

In asthma, chronic inflammatory processes in the airway play a centralrole in increasing the resistance to airflow within the lungs. Manycells and cellular elements are involved in the inflammatory process,particularly mast cells, eosinophils T lymphocytes, neutrophils,epithelial cells, and even airway smooth muscle itself. The reactions ofthese cells result in an associated increase in the existing sensitivityand hyper-responsiveness of the airway smooth muscle cells that line theairways to the particular stimuli involved.

The chronic nature of asthma can also lead to remodeling of the airwaywall (i.e., structural changes such as thickening or edema) which canfurther affect the function of the airway wall and influence airwayhyper-responsiveness. Other physiologic changes associated with asthmainclude excess mucus production, and if the asthma is severe, mucusplugging, as well as ongoing epithelial denudation and repair.Epithelial denudation exposes the underlying tissue to substances thatwould not normally come in contact with them, further reinforcing thecycle of cellular damage and inflammatory response.

In susceptible individuals, asthma symptoms include recurrent episodesof shortness of breath (dyspnea), wheezing, chest tightness, and cough.Currently, asthma is managed by a combination of stimulus avoidance andpharmacology.

Stimulus avoidance is accomplished via systematic identification andminimization of contact with each type of stimuli. It may, however, beimpractical and not always helpful to avoid all potential stimuli.

Asthma is managed pharmacologically by: (1) long term control throughuse of anti-inflammatories and long-acting bronchodilators and (2) shortterm management of acute exacerbations through use of short-actingbronchodilators. Both of these approaches require repeated and regularuse of the prescribed drugs. High doses of corticosteroidanti-inflammatory drugs can have serious side effects that requirecareful management. In addition, some patients are resistant to steroidtreatment. The difficulty involved in patient compliance withpharmacologic management and the difficulty of avoiding stimulus thattriggers asthma are common barriers to successful asthma management.Thus, current management techniques are neither completely successfulnor free from side effects.

In view of the foregoing, a non-pharmacological asthma treatment whichdoes not rely on avoiding stimuli is desirable.

SUMMARY OF THE INVENTION

The invention is a method for treating lung disease and in particular, amethod for treating the lung during an acute episode of reversibleobstructive pulmonary disease such as an asthma attack. One embodimentof the present invention includes a method for treating asthmacomprising the step of transferring energy to an airway wall of anairway in a lung such that a diameter of the airway is increased. Theenergy may be transferred to the airway wall prior to, during or afteran asthma attack. The energy may also be transferred in an amountsufficient to temporarily or permanently increase the effective diameterof the airway. The method may be performed while the airway is open,closed or partially closed.

In another embodiment of the invention, a method for treating asthma ina lung having a constricted airway comprises transferring energy to anairway wall of the constricted airway sufficient to open the airway. Theenergy transferred may be in an amount sufficient to permanently ortemporarily open the constricted airway. The method may be performed toopen a wholly constricted airway as well as a partly constricted airway.

In yet another variation of the invention, a method for treating lungdisease comprises transferring energy to an airway wall to alter theairway wall in such a manner that a resistance to airflow of the airwayis, decreased. The method may be performed by transferring energy toincrease the caliber of the airway. The airway wall may also be alteredby decreasing a thickness of the airway wall. The energy may betransferred to the airway wall during an asthma attack.

In another variation of the invention, the method comprises manipulatinga distal portion of an energy delivery apparatus to a first locationalong the airway prior to applying the energy. The energy deliveringapparatus can include a rounded tip sufficiently flexible such that whenthe tip encounters a closed or partially closed airway, trauma to theairway is minimized. The energy is then applied to a discrete locationwhile the distal portion of the energy delivery apparatus is stationary.The distal portion can then be moved to a new location and the processrepeated until a number of discrete locations have been treated. In analternative, the method comprises moving the distal portion of theenergy delivery apparatus from the first location and applying energywhile the distal portion is being moved in the airway.

In another variation of the present invention, a method comprisestransferring energy to or from an airway wall to treat a lung diseasesuch as asthma. The method may be carried out by inserting into theairway an apparatus having a cryogenic tip or other cooling meanscapable of transferring energy from the tissue, resulting in a desiredcondition such as a larger diameter airway.

In yet another variation of the invention, a combination of the abovediscussed techniques are carried out such that at one time, energy isapplied while the distal portion of the energy delivery device is beingmoved and at another time, energy is applied when the distal portion ofthe apparatus is stationary.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in greater detail with reference tothe various embodiments illustrated in the accompanying drawingswherein:

FIG. 1. is a cross sectional view of an airway in a healthy lung;

FIG. 2. shows a section through a bronchiole having an airway diametersmaller than that shown in FIG. 1;

FIG. 3 illustrates the airway of FIG. 1 in which the smooth muscle hashypertrophied and increased in thickness causing reduction of the airwaydiameter;

FIG. 4 is a schematic side view of the lungs being treated with atreatment device as described herein;

FIG. 5 is a partial view of an energy delivery device which can be usedto carry out the method of the invention; and

FIG. 6 is a partial view of a thermocouple attached to an energydelivering device in accordance with the invention.

DETAILED DESCRIPTION

This invention relates to methods for improving airflow through theairways of a lung having reversible obstructive pulmonary disease. Inaccordance with the invention an airway may be treated during an acuteepisode of reversible obstructive pulmonary disease such as an asthmaattack. The invention comprises applying or transferring energy to anairway wall to increase the diameter of the airway or otherwise reduceresistance to airflow through the airway. The energy may be transferredin an amount sufficient to temporarily or permanently increase thediameter of the airway. Notably, the method may be performed while theairway is open, closed or partially closed. The inventive method thuscan “rescue” an asthma sufferer during an acute asthma episode byincreasing the diameter of a constricted airway.

Various airways are shown in FIGS. 1-3. FIGS. 1 and 2 show a crosssection of two different airways in a healthy patient. The airway ofFIG. 1 is a medium sized bronchus having an airway diameter D1 of about3 mm. FIG. 2 shows a section through a bronchiole having an airwaydiameter D2 of about 1.5 mm. Each airway includes a folded inner surfaceor epithelium 10 surrounded by stroma 12 and smooth muscle tissue 14.The airway is thus quite different from other tissues such as bloodvessel tissue which does not include such folds. The larger airwaysincluding the bronchus shown in FIG. 1 also have mucous glands 16 andcartilage 18 surrounding the smooth muscle tissue 14. Nerve fibers 20and blood vessels 24 surround the airway.

FIG. 3 illustrates the bronchus of FIG. 1 in which the smooth muscle 14has hypertrophied and increased in thickness causing the airway diameterto be reduced from the diameter D1 to a diameter D3. Accordingly, theairways to be treated with the device of the present invention may be 1mm in diameter or greater. The airways to be treated are often second toeighth generation, and more preferably airways of the second to sixthgeneration.

FIG. 4 is an illustration of the lungs being treated with a system 36which can be used to carry out the present invention. The system 36includes a controller 32 and an energy treatment device 30 which may bean elongated member as described further below. The device 30 alsoincludes an expandable distal section which can be positioned at atreatment site 34 within a lung or another target medium. In operation,the device is manipulated to the treatment site 34. RF energy, forexample, is delivered through the energy delivering device andpenetrates the surface of the lung tissue such that tissue is affectedbelow the epithelial layer as well as on the surface of the lung tissue.The application of energy may cause a variety of structural andphysiological effects which may result from the application of energy tothe airway wall. For example, application of energy to the airway smoothmuscle of an asthmatic patient can debulk or otherwise reduce the volumeof smooth muscle. This reduced volume of smooth muscle increases theairway diameter for improved air exchange. Even small increases in theairway size can provide relief as the resistance to airflow variesinversely with approximately the fourth power of diameter.

Application of energy to an airway wall can also reduce inflammation inthe inner lung tissue. Reducing inflammation and edema of the tissuesurrounding the airway can increase the diameter of an airway.Inflammation and edema (accumulation of fluid) of the airway are chronicfeatures of asthma. The inflammation and edema can be reduced byapplication of energy to stimulate wound healing and regenerate normaltissue. Healing of the epithelium or sections of the epitheliumexperiencing ongoing denudation and renewal allows regeneration ofhealthy epithelium with less associated airway inflammation. The lessinflamed airway has an increased airway diameter both at a resting stateand in constriction. The wound healing can also deposit collagen whichimproves parenchymal tethering.

Application of energy to an airway wall can also inhibit the release ofinflammatory mediators in the airway wall which may serve as a stimulusfor airway smooth muscle contraction. Therapy that reduces theproduction and release of inflammatory mediators can reduce smoothmuscle contraction, inflammation of the airways, and edema. Examples ofinflammatory mediators are cytokines, chemokines, and histamine. Thetissues which produce and release inflammatory mediators include airwaysmooth muscle, epithelium, and mast cells. Thus, treatment of thesestructures with energy can reduce the ability of the airway structuresto produce or release inflammatory mediators. The reduction in releasedinflammatory mediators will reduce chronic inflammation, therebyincreasing the airway inner diameter, and may also reduce of the airwaysmooth muscle.

Application of energy to an airway wall can also increase the airwaydiameter by damaging nerve tissue in the airways. This follows because aresting tone of smooth muscle is nerve regulated by release ofcatecholamines. Thus, by damaging or eliminating nerve tissue in theairways the resting tone of the smooth muscle is reduced, and the airwaydiameter is increased.

Application of energy to the airways may cause other physiologicalresponses which result in increased diameters. It is to be understood,however, that the invention is not limited to a certain physiologicalresponse or process except where such a physiological response orprocess is a claim limitation in the appended claims.

As shown in FIG. 4, the present invention may be performed using acontroller 32 and a device 30 through which it delivers energy to thetarget medium 34. A device 30 of the present invention should be of asize to access the bronchus or bronchioles of the human lung. The devicemay be sized to fit within bronchoscopes, preferably, with bronchoscopeshaving a working channel of 2 mm or less. The device may also include asteering member configured to guide the device to a desired targetlocation. For example, this steering member may deflect a distal tip ofthe device in a desired direction to navigate to a desired bronchi orbronchiole.

Another aspect of the present invention is to treat more than onelocation. Several to many locations (e.g., reference numerals 31, 34 and38) in the airways may be treated in order to reduce asthmatic symptoms.This can be accomplished by manipulating or positioning the expandablebasket at a target site in the airways, expanding the expandable basketsuch that the energy transfer elements (e.g., the basket legs) contactthe airway wall, and then delivering energy to the airway wall. Theexpandable basket is preferably collapsed and moved to another locationand the process is repeated. This technique for applying energy atdiscrete locations can be repeated as many times as necessary to treatthe asthmatic symptoms.

The present invention also includes applying energy continuously alongan airway as an expanded basket is moved along the airway. Specifically,the basket may be deployed, energized, and then moved along the airwaycontinuously to continually transfer energy to or from the airway wallas the basket is moved axially along the airway. The above describedmethods may also be used in combination with one another.

An exemplary partial view of an energy delivering device which may beused to perform the invention is shown in FIG. 5. The energy deliveringapparatus 30 typically includes an elongate body having a proximalsection and a distal section. The distal section features a radiallyexpandable basket having a plurality of legs 106. The legs may beelectrodes or have an active region defined by an insulated coveringwhich contacts the medium to be treated. The basket is expanded with anactuator mechanism 112 which may be activated by a movable lever in ahandle attached to the proximal end of the elongate body.

The invention may also include an atraumatic tip 200 to ensure that theinvention does not injure airway tissue when it is placed into airwaysthat are partially or completely closed. The tip may be formed of aflexible material and/or may be rounded to minimize trauma. Examples ofenergy delivering devices in accordance with the present invention aredescribed in co-pending U.S. application Ser. No. 09/436,455 filed. Nov.8, 1999 which is hereby incorporated by reference in its entirety. Otherexamples of devices and methods which may be used in accordance with thepresent invention are found in the following U.S. patent applicationSer. No. 09/095,323—Methods and Apparatus for Treating Smooth Muscles inthe Walls of Body Conduits; Ser. No. 09/349,715—Method of Increasing GasExchange of a Lung; and Ser. No. 09/296,040—Devices for Modification ofAirways By Transfer of Energy. The entirety of each of theaforementioned applications is hereby incorporated by reference. Anothersuitable energy device is described in International patent applicationno PCT/US00/28745.

The energy delivery device may further comprise a temperature detectingelement. Examples of temperature detecting elements includethermocouples, infrared sensors, thermistors, resistance temperaturedetectors (RTDs), or any other apparatus capable of detectingtemperatures or changes in temperature. The temperature detectingelement is preferably placed in proximity to the expandable member.

FIG. 5 is a partial view of a variation of the energy delivery devicehaving thermocouple 137 positioned about midway along basket leg 106.FIG. 6 is an enlarged partial view of the thermocouple 137 of FIG. 5showing the leads 139 separately coupled on an inwardly-facing surfaceof the leg 106. Consequently, the basket leg itself is used as part ofthe thermocouple junction upon which the temperature measurement isbased. The thermocouple junction is intrinsic to the basket leg. Thisconfiguration is preferred because it provides an accurate temperaturemeasurement of tissue contacting the leg 106 in the vicinity of thethermocouple leads. In contrast, typical thermocouple configurationsconsist of a thermocouple junction offset or extrinsic to the basketleg. Thermocouple junctions offset or extrinsic to the basket leg do notmeasure temperature as accurately in certain applications asthermocouple junctions which are intrinsic to the basket leg.

An intrinsic thermocouple junction configuration is safer than anextrinsic thermocouple junction because, in the event one of thethermocouple leads separates from a basket leg, the intrinsicthermocouple junction becomes “open” and no thermocouple signal isproduced. In contrast, when an extrinsic thermocouple junction separatesfrom a basket leg a signal continues to be produced. The signal of adetached extrinsic thermocouple junction can be misleading becausealthough a temperature reading continues to be produced, the temperaturereading does not reflect the temperature at the point where the basketleg contacts the subject tissue. Accordingly, an intrinsic thermocouplejunction having two leads separately attached to a basket leg ispreferred.

FIG. 6 also shows basket leg 106 having an outer insulating material orcoating 410. The boundaries 415 of the insulating material 410 define anuninsulated, active section of electrode leg 106 which delivers energyto the airway walls. Preferably, the insulating coating 410 is heatshrink tubing or a polymeric coating. However, other insulatingmaterials may be used.

Various controllers may be used to carry out the invention. An exampleof an RF controller which may be used to carry out the invention isdescribed in co-pending International Patent Application No. PCT (notyet assigned), entitled “CONTROL SYSTEM AND PROCESS FOR APPLICATION OFENERGY TO AIRWAY WALLS AND OTHER MEDIUMS” filed Oct. 17, 2001incorporated herein by reference in its entirety.

The controller and power supply is configured to deliver enough energyto produce a desired effect in the lung. The power supply should also beconfigured to deliver the energy for a sufficient duration such that theeffect persists. This may be accomplished by a time setting which may beentered into the power supply memory by a user.

The power supply or generator may also employ a number of algorithms toadjust energy delivery, to compensate for device failures (such asthermocouple detachment), to compensate for improper use (such as poorcontact of the electrodes), and to compensate for tissue inhomogeneitieswhich can affect energy delivery such as, for example, subsurfacevessels, adjacent airways, or variations in connective tissue.

The power supply can also include circuitry for monitoring parameters ofenergy transfer: (for example, voltage, current, power, impedance, aswell as temperature from the temperature sensing element), and use thisinformation to control the amount of energy delivered. In the case ofdelivering RF energy, typical frequencies of the RF energy or RF powerwaveform are from 300 to 1750 kHz with 300 to 500 kHz or 450 to 475being preferred. The RF power-level generally ranges from about 0-30 Wbut depends upon a number of factors such as the size and number of theelectrodes. The controller may also be configured to independently andselectively apply energy to one or more of the basket leg electrodes.

A power supply may also include control modes for delivering energysafely and effectively. Energy may be delivered in open loop (power heldconstant) mode for a specific time duration. For example, a powersetting of 8 to 30 Watts for up to 10 seconds is suitable and a powersetting of 12 to 30 Watts for up to 5 seconds is preferred. For morepermanent restructuring of the airways, a power setting of 8 to 15 Wattsfor 5 to 10 seconds is suitable. For mere temporary relief orenlargement of the airway, a power setting of 10 to 25 Watts for up to 3seconds is suitable. With higher power settings, correspondingly lowertime durations are preferred to limit collateral thermal damage.

Energy may also be delivered in temperature control mode, with outputpower varied to maintain a certain temperature for a specific timeduration. For example, energy may be delivered for up to 20 seconds at atemperature of 55 to 80 degrees C., and more preferably, energy isdelivered up to 10 seconds at a temperature in the range of 60 to 70degrees C. For more permanent restructuring of the airways, energy isdelivered for 5 to 10 seconds at a temperature in the range of 60 to 70degrees C. For mere temporary relief or enlargement of the airway,energy is delivered for up to 5 seconds at a temperature of 55 to 80degrees. C. Additionally, the power supply may operate in impedancecontrol mode.

The operator may start at low values of power, temperature and time, andtreat until the desired effect (for example, airway diameter increasingor tissue blanching) is acutely observed, raising the power, temperatureor time as needed.

Notably, the methods of the invention may be performed while the lung isexperiencing natural symptoms of reversible obstructive pulmonarydisease. One such example is where an individual, experiencing an asthmaattack, or acute exacerbation of asthma or COPD, undergoes treatment toimprove the individual's ability to breath. In such a case, thetreatment provides immediate relief for (i.e., “rescues”) the patient.

All of the features disclosed in the specification (including anyaccompanying claims, abstract and drawings), and/or all of the steps ofany method or process disclosed, may be combined in any combination,except combinations where at least some of such features and/or stepsare mutually exclusive.

Each feature disclosed, in this specification (including anyaccompanying claims, abstract and drawings), may be replaced byalternative features serving the same, equivalent or similar purpose,unless expressly stated otherwise. Thus, unless expressly statedotherwise, each feature disclosed is one example only of a genericseries of equivalent or similar features.

The invention is not restricted to the details of the foregoingembodiments. The invention extends to any novel one, or any novelcombination, of the features disclosed in this specification (includingany accompanying claims, abstract and drawings), or to any novel one, orany novel combination, of the steps of any method or process sodisclosed.

1-32. (canceled)
 33. A system for treating a lung, the systemcomprising: an elongate assembly configured to move along an airway ofthe lung, the elongate assembly including an expandable distal portionhaving an electrically conductive region defined by an electricallynonconductive portion; and a controller coupled to the distal portion,the controller being configured to control energy delivery to the lungby the electrically conductive region to damage nerve tissue extendingalong the airway.
 34. The system of claim 33, wherein the controller isfurther configured to adjust the temperature of the electricallyconductive region to approximately 60 to 80 degrees C.
 35. The system ofclaim 34, further including a temperature detecting element coupled tothe distal portion.
 36. The system of claim 35, wherein the temperaturedetecting element is coupled to the electrically conductive region ofthe distal portion.
 37. The system of claim 36, wherein the temperaturedetecting element is coupled to the electrically conductive region ofthe distal portion by two leads.
 38. The system of claim 37, wherein,when one of the two leads of the temperature detecting element separatesfrom the electrically conductive region of the distal portion, notemperature signal is produced by the temperature detecting element. 39.The system of claim 33, wherein the electrically conductive region isconfigured to deliver RF energy.
 40. The system of claim 33, wherein thedistal portion includes a plurality of electrodes.
 41. The system ofclaim 40, wherein the controller is further configured to independentlyapply energy to one or more of the plurality of electrodes.
 42. Thesystem of claim 33, wherein the controller is further configured toutilize an impedance measurement to control energy delivery to thedistal portion.
 43. The system of claim 33, wherein the controller isconfigured to deliver energy to the distal portion for up to a specifictime duration.
 44. A system for treating a lung, the system comprising:an elongate assembly configured to move along an airway of the lung, theelongate assembly including a distal portion having a plurality ofelectrodes spaced about the distal portion; and a controller coupled tothe distal portion, the controller being configured to: control energydelivery to a first location in the lung by the distal portion to damagenerve tissue extending along the airway; terminate energy delivery; andreinitiate energy delivery after the distal portion has been moved to asecond location in the lung to damage nerve tissue at the secondlocation.
 45. The system of claim 44, wherein the plurality ofelectrodes are radially spaced about the distal portion and extendlongitudinally.
 46. The system of claim 44, wherein the controller isfurther configured to adjust the temperature of the electrodes toapproximately 60 to 80 degrees C.
 47. The system of claim 44, whereinthe controller is further configured to apply energy to one or more ofthe plurality of electrodes independent of the controller applyingenergy to the other of the plurality of electrodes.
 48. The system ofclaim 44, wherein the controller is further configured to utilize animpedance measurement to control energy delivery to the distal portion.49. The system of claim 44, wherein the distal portion is configured todeliver RF energy.
 50. A system for treating a lung, the systemcomprising: an elongate assembly configured to move along an airway ofthe lung, the elongate assembly including an expandable distal baskethaving a plurality of electrodes spaced about the distal basket, eachelectrode having an electrically conductive region defined by anelectrically nonconductive portion; and a controller coupled to thedistal basket, the controller being configured to: control energydelivery to a first location in the lung by the distal basket to damagenerve tissue extending along the airway; terminate energy delivery; andreinitiate energy delivery after the distal energy has been moved to asecond location in the lung to damage nerve tissue at the secondlocation.
 51. The system of claim 50, wherein the controller is furtherconfigured to apply energy to one or more of the plurality of electrodesindependent of the controller applying energy to the other of theplurality of electrodes.
 52. The system of claim 50, wherein thecontroller is further configured to utilize an impedance measurement tocontrol energy delivery to the distal basket.